A subset of prostate basal cells lacks the expression of corresponding phenotypic markers.
ABSTRACT Immunohistochemical staining for cytokeratin (CK) 34ssE12 has been routinely used to elucidate prostate basal cells for differentiation between non-invasive and invasive lesions. Our previous studies, however, revealed that some morphologically distinct basal cells observed on H&E-stained sections completely lacked CK34ssE12 expression. Our current study attempted to assess whether these basal cells would also lack the expression of other phenotypic markers, and whether basal cell alterations would affect the proliferation status of the associated tumor cells. Consecutive sections from prostate tumors with large basal cell clusters that were morphologically distinct in H&E sections but were completely negative for CK 34ssE12 were morphologically and immunohistochemically assessed with a panel of basal cell phenotypic and other markers. In addition to CK 34ssE12, these basal cells also completely lacked the expression of other phenotypic markers, including CK5, CK14, p63, and maspin, in contrast to adjacent basal cells, which were strongly positive for these markers. Tumors surrounded by basal cell layers that lack the expression of basal cell phenotypic markers showed a significantly higher rate of cell proliferation and mast cell infiltration than their counterparts. These findings suggest that basal cells might be targets of a variety of pathological alterations, which could significantly impact biological presentations of associated tumor cells.
- SourceAvailable from: Kenneth Iczkowski[Show abstract] [Hide abstract]
ABSTRACT: Despite advances in diagnosis and treatment of prostate cancer, development of metastases remains a major clinical challenge. Research efforts are dedicated to overcome this problem by understanding the molecular basis of the transition from benign cells to prostatic intraepithelial neoplasia (PIN), localized carcinoma, and metastatic cancer. Identification of proteins that inhibit dissemination of cancer cells will provide new perspectives to define novel therapeutics. Development of antimetastatic drugs that trigger or mimic the effect of metastasis suppressors represents new therapeutic approaches to improve patient survival. This review focuses on different biochemical and cellular functions of metastasis suppressors known to play a role in prostate carcinogenesis and progression. Ten putative metastasis suppressors implicated in prostate cancer are discussed. CD44s is decreased in both PIN and cancer; Drg-1, E-cadherin, KAI-1, RKIP, and SSeCKS show similar expression between benign epithelia and PIN, but are downregulated in invasive cancer; whereas, maspin, MKK4, Nm23 and PTEN are upregulated in PIN and downregulated in cancer. Moreover, the potential role of microRNA in prostate cancer progression, the understanding of the cellular distribution and localization of metastasis suppressors, their mechanism of action, their effect on prostate invasion and metastasis, and their potential use as therapeutics are addressed.Medicinal Research Reviews 09/2012; 32(5):1026-77. · 8.13 Impact Factor
- Prostate Biopsy, 12/2011; , ISBN: 978-953-307-702-4
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ABSTRACT: Prostatic lesions on routine staining sometimes cause diagnostic dilemma especially in premalignant lesions like atypical adenomatous hyperplasia and prostatic intraepithelial neoplasia. Benign small acinar lesions also may be difficult to differentiate from small acinar adenocarcinoma. An important differentiating point is the loss of basal cell layer in adenocarcinoma and its presence in benign lesions. Basal cell markers (e.g. 34βE12 cytokeratin) & proliferative markers (e.g. AgNOR and PCNA) can help in this regard. Total 60 cases of different prostatic lesions studied. After history taking, clinical examination, radiological & other investigations were done. Routine H&E staining, immunohistochemical staining against 34βE12 cytokeratin & proliferative markers (AgNOR & PCNA) was performed. Statistically significant differences found in expression of 34βE12 cytokeratin and proliferative markers between benign, premalignant and malignant prostatic lesions. Basal cell markers and proliferative markers are important parameters to distinguish between different benign, premalignant and malignant prostatic lesions.Indian Journal of Surgery 04/2011; 73(2):101-6. · 0.27 Impact Factor